Risk Factor and Prediction Modeling for Sudden Cardiac Death in Women With Coronary Artery Disease

Study Questions:

What are the predictors of sudden cardiac death (SCD) in women?


This analysis used data from the Heart and Estrogen/progestin Replacement Study (HERS), a randomized, double-blind, placebo-controlled trial of the effect of treatment with 0.25 mg of conjugated estrogens plus 2.50 mg of medroxyprogesterone acetate daily versus placebo on the coronary artery disease (CAD) event rate among postmenopausal women with documented CAD. The participants were postmenopausal women younger than 80 years with no previous hysterectomy and a history of at least one of the following: myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary angioplasty, or angiographic narrowing of a coronary artery of more than 50%. Women with New York Heart Association class III or IV heart failure were excluded. The primary outcome of interest, SCD, was defined as death resulting from a cardiac origin that occurred within 1 hour of symptom onset.


Of the 2,763 women enrolled in HERS, there were 254 cardiac deaths and 246 noncardiac deaths during the 6.8-year follow-up period. SCD made up 54% (136 events) of the cardiac-related deaths and 27% of all deaths, with an annual event rate of 0.79% per year (95% confidence interval, 0.67-0.94). Factors that were independently associated with SCD in multivariate analysis included myocardial infarction, heart failure, an estimated glomerular filtration rate of <40 ml/min/1.73 m2, atrial fibrillation, physical inactivity, and diabetes. The incidences of SCD among women with 0 (n = 683), 1 (n = 1,224), 2 (n = 610), and 3 plus (n = 246) risk factors at baseline were 0.3%, 0.5%, 1.2%, and 2.9% per year, respectively. The combination of clinical risk factors and left ventricular ejection fraction (LVEF) (C-index, 0.681) improved the prediction of SCD as compared to LVEF alone (C-index, 0.600) and resulted in an improvement in net reclassification (p < 0.001).


The investigators concluded that SCD comprised the majority of cardiac deaths among postmenopausal women with CAD. Independent predictors of SCD improved SCD prediction when considered with LVEF.


This analysis of the HERS study provides valuable information on SCD in women with CAD. If modification of any of these predictors results in reduced risk of SCD, it remains to be seen.

Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Coronary Artery Disease

Keywords: Progestins, Coronary Artery Disease, Myocardial Infarction, Medroxyprogesterone Acetate, Follow-Up Studies, Multivariate Analysis, Risk Reduction Behavior, Risk Factors, Angioplasty, New York, Estrogen Replacement Therapy, Death, Heart Failure, Hysterectomy, Stroke Volume, Ventricular Function, Glomerular Filtration Rate, Confidence Intervals, Coronary Artery Bypass, Diabetes Mellitus

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